title: Hydrogenase: a hydrogen-metabolizing enzyme. What do the crystal structures tell us about its mode of action?
abstract: Hydrogenases are proteins which metabolize the most simple of chemical compounds, molecular hydrogen, according to the reaction H2<-->2H+ + 2e-. These enzymes are found in many microorganisms of great biotechnological interest such as methanogenic, acetogenic, nitrogen fixing, photosynthetic or sulfate-reducing bacteria. The X-ray structure of a dimeric [NiFe] hydrogenase together with a wealth of biophysical, biochemical and genetic studies have revealed that the large subunit contains the bimetallic [Ni-Fe] active site, with biologically uncommon CO and CN ligands to the iron, whereas the small subunit contains three iron-sulfur cluster. During catalysis, the nickel atom is most likely responsible for a base-assisted heterolytic cleavage of the hydrogen molecule whereas the iron atom could be redox active. Specific channels are probably required for the transfer of the chemical reaction partners (H2, H+ and e-) between the active site, deeply buried inside the protein, and the molecular surface. The generation of a functional enzyme, including the assembly of the complex catalytic center, requires maturation and involves a large number of auxiliary proteins which have been partly characterized by molecular biology.
authors.affiliation: Laboratoire de Cristallographie et de Cristallogenèse des Protéines, Institut de Biologie Structurale Jean-Pierre-Ebel CEA-CNRS, Grenoble, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Fontecilla-Camps
authors.forename: M
authors.initials: M
authors.lastname: Frey
authors.forename: E
authors.initials: E
authors.lastname: Garcin
authors.forename: C
authors.initials: C
authors.lastname: Hatchikian
authors.forename: Y
authors.initials: Y
authors.lastname: Montet
authors.forename: C
authors.initials: C
authors.lastname: Piras
authors.forename: X
authors.initials: X
authors.lastname: Vernède
authors.forename: A
authors.initials: A
authors.lastname: Volbeda
mesh_terms: D018360:Crystallography, X-Ray; D003901:Desulfovibrio / Q000201:enzymology; D006859:Hydrogen / Q000378:metabolism; D006864:Hydrogenase / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D008667:Metalloproteins; D006859:Hydrogen; C043296:nickel-iron hydrogenase; D006864:Hydrogenase